Common Variable Immunodeficiency in New Zealand - Finding the Molecular and Cellular Foundations

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dc.contributor.advisor Woon, S en
dc.contributor.advisor Ameratunga, R en
dc.contributor.advisor Browett, P en
dc.contributor.author Koopmans, Wijntje en
dc.date.accessioned 2012-08-08T04:26:26Z en
dc.date.issued 2012 en
dc.identifier.uri http://hdl.handle.net/2292/19414 en
dc.description.abstract Common Variable Immunodeficiency Disorder (CVID) is a disorder characterised by low level of serum immunoglobulin and increased susceptibility to infection. The aim of this study was to develop a better understanding and prognosis for CVID patients. Clinical details and disease histories were analysed in 39 CVID patients. The time taken to diagnose CVID when symptoms first appear was in steady decline for the past 80 years. Those who develop CVID at a young age were more likely to develop bronchiectasis. Ten genes known to cause CVID in human or mouse were analysed in 95 patients (45 CVID, 50 hypogammaglobulinaemia). Thirty one SNPs and one deletion were identified with certain mutations already reported in literature. The following new mutations were identified: R20H and K186del in TACI; G42V in Bob-1; S77N in IL-15; T75M and N146T in IL-15Rα. The C104R mutation in TACI is linked to susceptibility to CVID. Segregation analysis was performed for a family with this mutation. Having one or both copies of the C104R allele is not a reliable predictor of CVID since the allele is not always present in family members with CVID. A healthy brother with the C104R/C104R genotype was identified. His markedly reduced immunoglobulin levels and reduced vaccine response requires close monitoring. The total CD8 central memory T cell or marginal zone B cell numbers could be potential health indicators in this family because these cell numbers are related to health status. B and T cell phenotyping were reported to predict clinical outcomes in CVID. The question is how consistent these assays are over time. The three B and one T cell assays were evaluated monthly over 6 and 3 months respectively. The EUROclass B cell classification system was the most consistent. CCR7 was the more reliable marker than CD62L for the memory T cell assay. Several potential markers for CVID were identified in this work. Certain cell subsets were significantly (p  0.01) elevated (CD38low CD21low B cells, transitional B cells, CD4+ effector memory T cells and CD4+ Tim3+) or decreased (switched memory B cells and CD4+ naïve T cells) compared to normal donors. en
dc.publisher ResearchSpace@Auckland en
dc.relation.ispartof PhD Thesis - University of Auckland en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.rights.uri http://creativecommons.org/licenses/by-nc-sa/3.0/nz/ en
dc.title Common Variable Immunodeficiency in New Zealand - Finding the Molecular and Cellular Foundations en
dc.type Thesis en
thesis.degree.grantor The University of Auckland en
thesis.degree.level Doctoral en
thesis.degree.name PhD en
dc.rights.holder Copyright: The author en
pubs.elements-id 360107 en
pubs.record-created-at-source-date 2012-08-08 en


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http://creativecommons.org/licenses/by-nc-sa/3.0/nz/ Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-sa/3.0/nz/

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